This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this study is to assess the safety and tolerability and pentosan polysulfate sodim in patients with sickle cell disease. Also, to assess the pharma-codynmic activity of PPS adminstered daily for three months. The activity of PPS on microvascular blood flow, vascular endothelial injury, and vas-occlusive pain associated with sickle cell disease will also be evaluated. This clinical investigation will utilize a multi-center, randomized, double-blind, placebo-contrrolled, parallel design. Eligible subjects will be male or female patients at least 18 years old with homozygous sickle cell anemia or sickle cell thalessemia. This study will comprise of a 3-week screening/baseline period, a 12-week treatment period, and 4-week follow up.